The overall aim of this K24 Mid-Career Investigator Award in Patient-Oriented Research is to allow Dr. Frances Levin to continue to expand her programmatic line of clinical research and mentoring. Three objectives drive the applicant's work: 1) develops pharmacotherapies that consider the heterogeneity of substance abusers 2) provides mentorship to junior clinical investigators, and 3) contribute service to the field. Primary activities and accomplishments include promoting the recognition and treatment of adult attention- deficit hyperactivity in substance abusers, developing novel combined medication treatment strategies for cocaine and cannabis-dependent individuals, and pursuing promising medications combined with motivational and behavioral treatments for cannabis dependence. During the course of the award Dr. Levin will be PI of 3 RO1s (two are multi-site controlled trials) and PI of a T32 that targets the training of physicians. Additionally, she will continue to serve as the PI of a major R01-equivalent project investigating a combined pharmacotherapy for cannabis dependence and serve as the Director of the Education Core of a long-standing Medications Development Center. Further, she will serve as a Co-PI or Co-I on several other RO1s with both junior and mid-career colleagues that extend her areas of interest. The career development plan for this application will expand Dr. Levin's knowledge into the areas of molecular genetics and neurocognition through accessing the expertise of specialists in these areas. The mentoring plan incorporates trainees at various levels of development: 1) pre-doctoral trainees;2) post- doctoral trainees (psychiatric residents or substance abuse research fellows);and 3) junior faculty. An overarching career goal has been to train and mentor clinical investigators and advance knowledge in the substance abuse field through synergistic collaborations with other investigators, often with individuals that Dr. Levin has mentored or is currently mentoring. The research and mentoring plan has major public health significance. Substance abuse is often accompanied with additional psychiatric comorbidity and effective treatments for comorbid individuals remain elusive. Moreover, there has been minimal research evaluating pharmacotherapies for cannabis dependence, despite its substantial morbidity. Of great public concern is a dearth of adequately trained physician- investigators interested in clinical substance abuse research careers. Through Dr. Levin's activities it is hoped that the treatment of substance abusers will improve, both through her research and collaborations with colleagues, and through her training of the next generation of clinical investigators. PUBLIC HEALTH RELEVANCE: The objectives of this patient-oriented K24 proposal is to gain greater knowledge of novel treatment options for substance use disorders as well as possible vulnerabilities that might place certain populations at risk for substance abuse and impede treatment efficacy. These goals address a critical public health need and will be attained through the applicant's programmatic line of patient-oriented research and her mentorship of trainees, junior faculty, and other mentees such that they obtain the necessary research skills to pursue independent clinical research careers.